Aripiprazole Augmentation in Major Depressive Disorder: A Double-Blind, Placebo-Controlled Study in Patients with Inadequate Response to Antidepressants

CNS Spectrums ◽  
2009 ◽  
Vol 14 (4) ◽  
pp. 197-206 ◽  
Author(s):  
Robert M. Berman ◽  
Maurizio Fava ◽  
Michael E. Thase ◽  
Madhukar H. Trivedi ◽  
René Swanink ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Symptoms ◽  
Adverse Events ◽  
Depressive Disorder ◽  
Controlled Study ◽  
Inadequate Response ◽  
Completion Rates ◽  
Madrs Total Score ◽  
Major Depressive ◽  
Double Blind

ABSTRACTIntroduction: Effective management of major depressive disorder (MDD) continues to be a challenging task for psychiatrists and primary care physicians. This trial evaluated the efficacy and safety of adjunctive aripiprazole versus antidepressant monotherapy in patients with MDD and independently replicated the positive findings of two similar trials.Methods: Patients (N=1, 147) with MDD experiencing a major depressive episode and a history of inadequate response to antidepressant monotherapy were enrolled (week 0); 827 received single-blind adjunctive placebo plus open-label antidepressant (escitalopram, fluoxetine, paroxetine controlled release, sertraline, or venlafaxine extended release) for 8 weeks to confirm inadequate response to antidepressants; 349 patients with inadequate response were randomized (1:1) to double-blind, adjunctive placebo (n=172) or adjunctive aripiprazole (n=177; 2–20 mg/day). Primary outcome was the mean change in Montgomery-Åsberg Depression Rating Scale (MADRS) Total score from baseline (week 8) to endpoint (week 14).Results: Clinically significant improvements in depressive symptoms as assessed by decreases in the MADRS Total score were greater with adjunctive aripiprazole (−10.1) than placebo (−6.4; P<.001). Remission rates were greater for adjunctive aripiprazole than for adjunctive placebo (week 14, 36.8% vs 18.9%; P<.001). Completion rates with adjunctive aripiprazole and placebo were high (83% vs. 87%) and discontinuations due to adverse events were low (6.2% vs 1.7%).Conclusion: For some patients with MDD who do not obtain adequate symptom relief with antidepressant monotherapy, adjunctive therapies can significantly improve depressive symptoms. As reported, adjunctive aripiprazole was associated with a two-fold higher remission rate than adjunctive placebo. This, and previous studies, have shown that discontinuations due to adverse events were low and completion rates were high, and has indicated that both antidepressant and aripiprazole in combination were relatively well-tolerated and safe. This is the third consecutive clinical trial, in the absence of a failed trial, to demonstrate that aripiprazole augmentation to antidepressants is an efficacious and well-tolerated treatment for patients with MDD who do not respond adequately to standard antidepressant monotherapy (ClinicalTrials.gov study NCT00105196).

Omega-3 as an adjunctive therapy of sertraline and venlafaxine substantially improves symptoms of major depressive disorder: A double-blind, placebo-controlled study

2021 ◽  
Vol 10 ◽  
Author(s):  
Mohammad Ahadifard Moghaddam ◽  
Malihe Farid ◽  
Mahboobeh Mehrabani Natanzi ◽  
Zohre Khodaii ◽  
Rahim Badrfam ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Symptoms ◽  
Depressive Disorder ◽  
Controlled Study ◽  
P Value ◽  
Omega 3 ◽  
Major Depressive ◽  
Double Blind ◽  
Double Blind Clinical Trial ◽  
Severity Of Depression

Background: Due to the possible effect of omega-3 fatty acids on reducing depressive symptoms, in this study, we investigated these effects in combination with other antidepressants. Methods: The study was a double-blind clinical trial on 100 patients with major depressive disorder who were divided into four groups of 25 each and treated with 50 mg daily sertraline plus placebo, 50 mg daily sertraline plus two grams Omega 3 daily, 75 mg daily venlafaxine plus placebo, and 75 mg daily venlafaxine plus 2 g Omega 3 daily for 6 weeks. Results: The mean Hamilton depression rating score of sertraline and venlafaxine plus omega-3 after treatment were 4.42 and 4.23 respectively versus sertraline and venlafaxine plus placebo 14.4 and 14.2 respectively (P value=0.0001). Conclusion: Omega-3 enhanced the clinical function of sertraline and venlafaxine to reduce the severity of depression. Adding omega-3 to either sertraline or venlafaxine does not have a comparative advantage over each other in terms of the improvement of severity of depressive symptoms. Trial registration : number is IRCT20190302042885N1.

scholarly journals Efficacy of adjunctive aripiprazole in patients with major depressive disorder whose symptoms worsened with antidepressant monotherapy

CNS Spectrums ◽  
2014 ◽  
Vol 19 (6) ◽  
pp. 528-534 ◽  
Author(s):  
J. Craig Nelson ◽  
Zia Rahman ◽  
Kimberly K. Laubmeier ◽  
James M. Eudicone ◽  
Robert D. McQuade ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Rating Scale ◽  
Response Rates ◽  
Antipsychotic Treatment ◽  
Inadequate Response ◽  
Madrs Total Score ◽  
Major Depressive ◽  
Double Blind ◽  
Remission Rates

IntroductionEfficacy of depression treatments, including adjunctive antipsychotic treatment, has not been explored for patients with worsening symptoms after antidepressant therapy (ADT).MethodsThis post-hoc analysis utilized pooled data from 3 similarly designed, randomized, double-blind, placebo-controlled trials that assessed the efficacy, safety, and tolerability of adjunctive aripiprazole in patients with major depressive disorder with inadequate response to ADT. The studies had 2 phases: an 8-week prospective ADT phase and 6-week adjunctive (aripiprazole or placebo) treatment phase. This analysis focused on patients whose symptoms worsened during the prospective 8-week ADT phase (worsening defined as >0% increase in Montgomery–Åsberg Depressive Rating Scale [MADRS] Total score). During the 6-week, double-blind, adjunctive phase, response was defined as ≥50% reduction in MADRS Total score and remission as ≥50% reduction in MADRS Total score and MADRS score ≤10.ResultsOf 1065 patients who failed to achieve a response during the prospective phase, 160 exhibited worsening of symptoms (ADT-Worseners), and 905 exhibited no change/reduction in MADRS scores (ADT-Non-worseners). Response rates for ADT-Worseners at endpoint were 36.6% (adjunctive aripiprazole) and 22.5% (placebo). Similarly, response rates at endpoint for ADT-Non-worseners were 37.5% (adjunctive aripiprazole) and 22.5% (placebo). Remission rates at endpoint for ADT-Worseners were 25.4% (adjunctive aripiprazole) and 12.4% (placebo). For ADT-Non-worseners, remission rates were 29.9% (adjunctive aripiprazole) and 17.4% (placebo).ConclusionThese results suggest that adjunctive aripiprazole is an effective intervention for patients whose symptoms worsen during antidepressant monotherapy. The results challenge the view that benefits of adjunctive therapy with aripiprazole are limited to partial responders to ADT.

scholarly journals Beneficial and harmful effects of antidepressants versus placebo, ‘active placebo’, or no intervention for adults with major depressive disorder: a protocol for a systematic review of published and unpublished data with meta-analyses and trial sequential analyses

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Sophie Juul ◽  
Faiza Siddiqui ◽  
Marija Barbateskovic ◽  
Caroline Kamp Jørgensen ◽  
Michael Pascal Hengartner ◽  
...  
Keyword(s):  
Systematic Review ◽  
Major Depressive Disorder ◽  
Depressive Symptoms ◽  
Adverse Events ◽  
Depressive Disorder ◽  
Meta Analysis ◽  
Risk Of Bias ◽  
Major Depressive ◽  
Serious Adverse Events ◽  
Harmful Effects

Abstract Background Major depressive disorder is one of the most common, burdensome, and costly psychiatric disorders worldwide. Antidepressants are frequently used to treat major depressive disorder. It has been shown repeatedly that antidepressants seem to reduce depressive symptoms with a statistically significant effect, but the clinical importance of the effect sizes seems questionable. Both beneficial and harmful effects of antidepressants have not previously been sufficiently assessed. The main objective of this review will be to evaluate the beneficial and harmful effects of antidepressants versus placebo, ‘active placebo’, or no intervention for adults with major depressive disorder. Methods/design A systematic review with meta-analysis will be reported as recommended by Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA), bias will be assessed with the Cochrane Risk of Bias tool-version 2 (ROB2), our eight-step procedure will be used to assess if the thresholds for clinical significance are crossed, Trial Sequential Analysis will be conducted to control for random errors, and the certainty of the evidence will be assessed with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. To identify relevant trials, we will search both for published and unpublished trials in major medical databases from their inception to the present. Clinical study reports will be obtained from regulatory authorities and pharmaceutical companies. Two review authors will independently screen the results of the literature searches, extract data, and perform risk of bias assessment. We will include any published or unpublished randomised clinical trial comparing one or more antidepressants with placebo, ‘active placebo’, or no intervention for adults with major depressive disorder. The following active agents will be included: agomelatine, amineptine, amitriptyline, bupropion, butriptyline, cianopramine, citalopram, clomipramine, dapoxetine, demexiptiline, desipramine, desvenlafaxine, dibenzepin, dosulepin, dothiepin, doxepin, duloxetine, escitalopram, fluoxetine, fluvoxamine, imipramine, iprindole, levomilnacipran, lofepramine, maprotiline, melitracen, metapramine, milnacipran, mirtazapine, nefazodone, nortriptyline, noxiptiline, opipramol, paroxetine, protriptyline, quinupramine, reboxetine, sertraline, trazodone, tianeptine, trimipramine, venlafaxine, vilazodone, and vortioxetine. Primary outcomes will be depressive symptoms, serious adverse events, and quality of life. Secondary outcomes will be suicide or suicide attempt, suicidal ideation, and non-serious adverse events. Discussion As antidepressants are commonly used to treat major depressive disorder in adults, a systematic review evaluating their beneficial and harmful effects is urgently needed. This review will inform best practice in treatment and clinical research of this highly prevalent and burdensome disorder. Systematic review registration PROSPERO CRD42020220279

A randomised, placebo-controlled 24-week study evaluating adjunctive brexpiprazole in patients with major depressive disorder

2018 ◽  
Vol 31 (1) ◽  
pp. 27-35 ◽  
Author(s):  
Michael Bauer ◽  
Nanco Hefting ◽  
Annika Lindsten ◽  
Mette Krog Josiassen ◽  
Mary Hobart
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Treatment Period ◽  
Study Design ◽  
Primary Endpoint ◽  
Inadequate Response ◽  
Madrs Total Score ◽  
Open Label ◽  
Major Depressive ◽  
Full Remission

AbstractObjectiveTo evaluate brexpiprazole adjunctive to antidepressant therapies (ADTs) as maintenance treatment in patients with major depressive disorder with inadequate response to ADT, utilising a novel study design.MethodsThe study comprised an 8-week prospective treatment period with open-label ADT with double-blind placebo treatment and a 24-week randomised treatment period. Investigators and patients were blinded to treatment periods, randomisation criteria, and timing of randomisation. Patients with early response to open-label ADT were withdrawn at Week 6. Patients fulfilling criteria for inadequate response were randomised to ADT+brexpiprazole 1–3 mg/day, or ADT+placebo. The primary endpoint was full remission: Montgomery–Åsberg Depression Rating Scale (MADRS) total score ≤10 and ≥50% decrease from randomisation (i.e. baseline) in MADRS total score for at least 8 consecutive weeks.ResultsThe primary efficacy analysis failed to show a statistically significant difference between the proportions of patients on ADT+brexpiprazole (21.4%) and ADT+placebo (24.9%) achieving full remission; odds ratio: 0.83; p=0.2641. The secondary endpoint of change from baseline to Week 6 in MADRS total score showed no difference between ADT+brexpiprazole and ADT+placebo (−0.4; p=0.3259). The most frequent treatment-emergent adverse event (TEAE) in patients receiving ADT+brexpiprazole was weight increased (9.5% vs. 5.0% in ADT+placebo). The incidence of TEAEs leading to withdrawal in the randomised treatment period was 6.3% in the ADT+brexpiprazole group and 3.4% in the ADT+placebo group.ConclusionAdjunctive brexpiprazole did not differentiate from ADT+placebo on the primary endpoint of full remission. A number of design elements in this previously untried study design may have contributed to the study result. Brexpiprazole was well tolerated.

scholarly journals Lurasidone for the Treatment of Major Depressive Disorder With Mixed Features: A Randomized, Double-Blind, Placebo-Controlled Study

2016 ◽  
Vol 173 (4) ◽  
pp. 400-407 ◽  
Author(s):  
Trisha Suppes ◽  
Robert Silva ◽  
Josephine Cucchiaro ◽  
Yongcai Mao ◽  
Steven Targum ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Controlled Study ◽  
Major Depressive ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Mixed Features
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